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Background: Pelvic organ prolapse (POP) is a major health problem in adult women that involves many factors.No proteomic analysis has been conducted exclusively in POP patients.This study aimed to identify the differential expression of proteins that may be involved in POP by proteomic analysis.Methods: Samples of the uterosacral ligament (USL) were collected from five POP patients and five non-POP patients matched according to age, parity, and menopausal status and analyzed using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the mRNA expression of proteins that showed differential expression in the proteomic analyses.Results: Proteins differentially expressed between POP and non-POP patients were detected.Eight proteins that were down-regulated in the POP group were identified by MALDI-TOF-MS.These proteins included electron transfer flavoprotein, apolipoprotein A-I, actin, transgelin, cofilin-1, cyclophilin A, myosin, and galectin-1, and their expression was verified by qRT-PCR.Conclusion: Using comparative proteomics, we identified eight differentially expressed proteins (including four cytoskeleton proteins and three proteins related to apoptosis) in the USL that may be involved in apoptosis associated with the tissue effects in POP pathophysiology.